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Article Dans Une Revue Tetrahedron Année : 2021

Convenient approach for the synthesis of ONO-LB-457, a potent leukotriene B4 receptor antagonist

Résumé

This study reports a new approach for the synthesis of 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-(5E)-hexen-1-yloxy]phenoxy]pentanoic acid V (ONO-LB-457), previously described by Konno and col. and which is considered a highly potent and orally active LTB₄ receptor antagonist. This compound acts as an inhibitor of aggregation and chemotaxis, in addition to LTB₄-induced human neutrophil degranulation.In this work, the preparation of ONO-LB-457 was proposed through a convergent synthesis focused on the preparation of two fragments. First, the preparation of 5-hydroxychroman-2-one (4) from 2,6-dimethoxybenzaldehyde and malonic acid, involving a Knoevenagel reaction, followed by a reduction of the olefin and intramolecular cyclization catalyzed by Lewis acid (tribromide) was achieved with an overall yield of 57%. Second, preparation of (E)-6-(4-methoxyphenyl)hex-5-en-1-yl-methanesulfonate (18) from 5-bromovaleric acid (15) involving a Wittig reaction. The desired compound V (ONO-LB-457) was obtained by nucleophilic substitution of (E)-6-(4-methoxyphenyl)hex-5-en-1-yl-methanesulfonate (18) with the ring-opened phenolic diester 14 followed by hydrolysis, in seven steps with an overall yield of about 11%.
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hal-03493665 , version 1 (02-01-2023)

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Paternité - Pas d'utilisation commerciale

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Salha Hamri, Jabrane Jouha, Asmaa Oumessaoud, M.D. Pujol, Mostafa Khouili, et al.. Convenient approach for the synthesis of ONO-LB-457, a potent leukotriene B4 receptor antagonist. Tetrahedron, 2021, 77, pp.131740 -. ⟨10.1016/j.tet.2020.131740⟩. ⟨hal-03493665⟩
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